Is Hinokitiol Efficacious Against an Antimicrobial-Resistant Strain of Streptococcus pyogenes? A Research Protocol

Abstract

Introduction: Streptococcus pyogenes, a highly infectious and deadly gram-positive bacterium in the Group A Streptococcus family, that causes respiratory and skin infections. Treatments include oral penicillin and macrolides; however, penicillin and macrolide-resistant Streptococcus pyogenes (e.g., A458) are emerging. Hinokitiol, beta-thujaplicin, has been thought to be an alternative solution to help fight against antimicrobial resistant strains of S. pyogenes as several studies have highlighted its bactericidal effects. These effects in turn, inhibit the production of bacterial adenosine triphosphate and bacteriostatic effects (growth inhibition) of hinokitiol on a related bacterium, Streptococcus pneumoniae and a variant of Streptococcus pyogenes, SSI-9. Furthermore, hinokitiol was found to be very efficacious against a penicillin and macrolide resistant gram-positive bacterium, indicating that penicillin and macrolides likely have a different mechanism of action from hinokitiol. This suggests that microbes are likely not resistant to hinokitiol. Therefore, by extrapolating this data, it is thought that hinokitiol may be efficacious in combatting A458, a concerning antimicrobial resistant strain of Streptococcus pyogenes.

Methods: Every step would be performed under triple-blind conditions. Using a solvent control, penicillin G, streptomycin, and hinokitiol, an efficacy trial would be undertaken to evaluate the bactericidal/inhibitory effects of each drug and determine whether hinokitiol is superior to the current gold-standards. A two-way analysis of variance and multiple repeated-measures analysis of variance will be used to evaluate efficacy.

Results: It is expected that hinokitiol is efficacious against the resistant strain of Streptococcus pyogenes, A458 unlike streptomycin.

Discussion: The strengths of this study are that a novel treatment was used and the experiment was conducted as a triple-blinded experiment. The limitations include its efficiency and the lack of knowledge of the treatment. The statistical test conducted for this study would evaluate whether hinokitiol has a statistically significant effect on a resistant strain of Streptococcus pyogenes.

Conclusion: It is likely that hinokitiol will show a resistance-free effect on the two strains of Streptococcus pyogenes. This is a significant undertaking due to the dangers of antimicrobial-resistant Streptococcus pyogenes. However, further experiments need to be conducted to support this hypothesis.